2-{3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-4-methyl-1,3-thiazol-3-ium-5-yl}ethyl hydrogen phosphate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

A Toxicity Study of Parenteral Thiamine Hydrochloride

Author:

Wrenn et al.

Year:

1989

Bibliographic source:

Ann Emerg Med. 18:867-870

Materials and methods

Endpoint addressed:

other: repeated dose toxicity: other routes

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

The safety of the test substance was evaluated after administration intravenously as a 100 mg bolus in 989 consecutive patients. In total 1070 doses were administered. Four patients received large-dose thiamine for overt Wernicke's encephalopathy; two received 1 g in multiple 100 mg boluses and two received 300 mg in multiple 100 mg boluses within the first few hours of being seen. For purposes of analysis, these were considered single doses. There were 39 instances (3.9% of the total population) in which individual patients received between two and seven individual doses over the entire study period. One patient received seven doses, two received six, three received five, two received four, 16 received three, and 15 received two doses.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Thiamine hydrochloride

EC Number:

200-641-8

EC Name:

Thiamine hydrochloride

Cas Number:

67-03-8

Molecular formula:

C12H17N4OS.ClH.Cl

IUPAC Name:

3-[(4-amino-2-methylpyrimidin-5-yl)methyl]-5-(2-hydroxyethyl)-4-methyl-1,3-thiazol-3-ium chloride hydrochloride

Method

Type of population:

other: patients

Subjects:

- Number of subjects exposed: 989 patients
- Sex: 795 men (80%) and 194 women (20%)
- Age: 16 - 80 years
- Known diseases: alcoholism (65%), alcohol withdrawal (0.9%), alcoholic seizure (13%), alcoholic hypoglycemia (0.8%), seizures (7%), hypoglycemia (1%), hypothermia (1%), malnutrition (0.3%), cancer (0.1%), cocaine (0.2%), AIDS (0.8%), altered mental status (0.9%), sepsis ( 0.1%), drug overdose (0.7%), dehydration (0.2%), hypertension (0.1%), nausea or vomiting (0.5%), cerebrovascular accident (0.2%) and unknown (7%)

Ethical approval:

confirmed, but no further information available

Route of exposure:

other: intravenous (IV bolus)

Reason of exposure:

intentional

Details on exposure:

Over a 6-month period, 1070 doses of the test substance were administered by rapid IV push technique to 989 patients. Four patients received large-dose thiamine for overt Wernicke's encephalopathy; two received 1 g in multiple 100 mg boluses and two received 300 mg in multiple 100 mg boluses within the first few hours of being seen. For purposes of analysis, these were considered single doses

Examinations:

Cardiac monitor: 94 patients were incidentally on a cardiac monitor at the time of the study.

Results and discussion

Clinical signs:

Adverse reactions were observed in 12 cases (1.1%). In 11 of the cases, transient burning occurred immediately after injection in the arm with the IV line and lasted from seconds to minutes. The authors considered this a minor reaction with no allergic or immune component. Of these 11 patients, seven were men and four were women (1.75:1 ratio). The 12th case, transient generalized pruritus without any other associated symptoms was observed in the patient; the authors considered this a potentially major reaction. The rates of minor and major reactions, therefore, were 1.02 and 0.093%, respectively. No adverse systemic effects were reported.

Results of examinations:

Cardiac monitor: No arrhythmias were noted.